Evaluation of left ventricular and left atrial volumetric function from native MR multislice 4D flow magnitude data.

OBJECTIVES: To assess the feasibility, precision, and accuracy of left ventricular (LV) and left atrial (LA) volumetric function evaluation from native magnetic resonance (MR) multislice 4D flow magnitude images. MATERIALS & METHODS: In this prospective study, 60 subjects without signs or symptoms of heart failure underwent 3T native cardiac MR multislice 4D flow and bSSFP-cine realtime imaging. LV and LA volumetric function parameters were evaluated from 4D flow magnitude (4D flow-cine) and bSSFP-cine data using standard software to obtain end-diastolic volume (EDV), end-systolic volume (ESV), ejection-fraction (EF), stroke-volume (SV), LV muscle mass (LVM), LA maximum volume, LA minimum volume, and LA total ejection fraction (LATEF). Stroke volumes derived from both imaging methods were further compared to 4D pulmonary artery flow-derived net forward volumes (NFV). Methods were compared by correlation and Bland-Altman analysis. RESULTS: Volumetric function parameters from 4D flow-cine and bSSFP-cine showed high to very high correlations (r = 0.83-0.98). SV, LA volumes and LATEF did not differ between methods. LV end-diastolic and end-systolic volumes were slightly underestimated (EDV: -2.9 ± 5.8 mL; ESV: -2.3 ± 3.8 mL), EF was slightly overestimated (EF: 0.9 ± 2.6%), and LV mass was considerably overestimated (LVM: 39.0 ± 11.4 g) by 4D flow-cine imaging. SVs from both methods correlated very highly with NFV (r = 0.91 in both cases) and did not differ from NFV. CONCLUSION: Native multislice 4D flow magnitude data allows precise evaluation of LV and LA volumetric parameters; however, apart from SV, LV volumetric parameters demonstrate bias and need to be referred to their respective normal values. CLINICAL RELEVANCE STATEMENT: Volumetric function assessment from native multislice 4D flow magnitude images can be performed with routinely used clinical software, facilitating the application of 4D flow as a one-stop-shop functional cardiac MR exam, providing consistent, simultaneously acquired, volume and flow data. KEY POINTS: • Native multislice 4D flow imaging allows evaluation of volumetric left ventricular and atrial function parameters. • Left ventricular and left atrial function parameters derived from native multislice 4D flow data correlate highly with corresponding standard cine-derived parameters. • Multislice 4D flow-derived volumetric stroke volume and net forward volume do not differ.

Fine-Tuning Cardiac Insulin-Like Growth Factor 1 Receptor Signaling to Promote Health and Longevity.

BACKGROUND: The insulin-like growth factor 1 (IGF1) pathway is a key regulator of cellular metabolism and aging. Although its inhibition promotes longevity across species, the effect of attenuated IGF1 signaling on cardiac aging remains controversial. METHODS: We performed a lifelong study to assess cardiac health and lifespan in 2 cardiomyocyte-specific transgenic mouse models with enhanced versus reduced IGF1 receptor (IGF1R) signaling. Male mice with human IGF1R overexpression or dominant negative phosphoinositide 3-kinase mutation were examined at different life stages by echocardiography, invasive hemodynamics, and treadmill coupled to indirect calorimetry. In vitro assays included cardiac histology, mitochondrial respiration, ATP synthesis, autophagic flux, and targeted metabolome profiling, and immunoblots of key IGF1R downstream targets in mouse and human explanted failing and nonfailing hearts, as well. RESULTS: Young mice with increased IGF1R signaling exhibited superior cardiac function that progressively declined with aging in an accelerated fashion compared with wild-type animals, resulting in heart failure and a reduced lifespan. In contrast, mice with low cardiac IGF1R signaling exhibited inferior cardiac function early in life, but superior cardiac performance during aging, and increased maximum lifespan, as well. Mechanistically, the late-life detrimental effects of IGF1R activation correlated with suppressed autophagic flux and impaired oxidative phosphorylation in the heart. Low IGF1R activity consistently improved myocardial bioenergetics and function of the aging heart in an autophagy-dependent manner. In humans, failing hearts, but not those with compensated hypertrophy, displayed exaggerated IGF1R expression and signaling activity. CONCLUSIONS: Our findings indicate that the relationship between IGF1R signaling and cardiac health is not linear, but rather biphasic. Hence, pharmacological inhibitors of the IGF1 pathway, albeit unsuitable for young individuals, might be worth considering in older adults.

MR 4D flow-derived left atrial acceleration factor for differentiating advanced left ventricular diastolic dysfunction.

OBJECTIVES: The magnetic resonance (MR) 4D flow imaging-derived left atrial (LA) acceleration factor α was recently introduced as a means to non-invasively estimate LA pressure. We aimed to investigate the association of α with the severity of left ventricular (LV) diastolic dysfunction using echocardiography as the reference method. METHODS: Echocardiographic assessment of LV diastolic function and 3-T cardiac MR 4D flow imaging were prospectively performed in 94 subjects (44 male/50 female; mean age, 62 ± 12 years). LA early diastolic peak outflow velocity (vE), systolic peak inflow velocity (vS), and early diastolic peak inflow velocity (vD) were evaluated from 4D flow data. α was calculated from α = vE / [(vS + vD) / 2]. Mean parameter values were compared by t-test; diagnostic performance of α in predicting diastolic (dys)function was investigated by receiver operating characteristic curve analysis. RESULTS: Mean α values were 1.17 ± 0.14, 1.20 ± 0.08, 1.33 ± 0.15, 1.77 ± 0.18, and 2.79 ± 0.69 for grade 0 (n = 51), indeterminate (n = 9), grade I (n = 13), grade II (n = 13), and grade III (n = 8) LV diastolic (dys)function, respectively. α differed between subjects with non-advanced (grade < II) and advanced (grade ≥ II) diastolic dysfunction (1.20 ± 0.15 vs. 2.16 ± 0.66, p < 0.001). The area under the curve (AUC) for detection of advanced diastolic dysfunction was 0.998 (95% CI: 0.958-1.000), yielding sensitivity of 100% (95% CI: 84-100%) and specificity of 99% (95% CI: 93-100%) at cut-off α ≥ 1.58. The AUC for differentiating grade III diastolic dysfunction was also 0.998 (95% CI: 0.976-1.000) at cut-off α ≥ 2.14. CONCLUSION: The 4D flow-derived LA acceleration factor α allows grade II and grade III diastolic dysfunction to be distinguished from non-advanced grades as well as from each other. CLINICAL RELEVANCE STATEMENT: As a single continuous parameter, the 4D flow-derived LA acceleration factor α shows potential to simplify the multi-parametric imaging algorithm for diagnosis of advanced LV diastolic dysfunction, thereby identifying patients at increased risk for cardiovascular events. KEY POINTS: • Detection of advanced diastolic dysfunction is typically performed using a complex, multi-parametric approach. • The 4D flow-derived left atrial acceleration factor α alone allows accurate detection of advanced left ventricular diastolic dysfunction. • As a single continuous parameter, the left atrial acceleration factor α could simplify the diagnosis of advanced diastolic dysfunction.

Transesophageal echocardiography-guided versus fluoroscopy-guided patent foramen ovale closure: A single center registry.

BACKGROUND: Percutaneous closure of patent foramen ovale (PFO) is conventionally performed under continuous transesophageal echocardiographic (TEE) guidance. We aimed to evaluate whether a simplified procedural approach, including pure fluoroscopy-guidance and final TEE control, as well as an aimed 'next-day-discharge' is comparable with the conventional TEE-guided procedure in terms of periprocedural and intermediate-term outcomes. METHODS: All patients who underwent a PFO closure at our center between 2010 and 2022 were retrospectively included. Prior to June 2019 cases were performed with continuous TEE guidance (TEE-guided group). Since June 2019, only pure fluoroscopy-guided PFO closures have been performed with TEE insertion and control just prior to device release (fluoroscopy-guided group). We analyzed procedural aspects, as well as long term clinical and echocardiographic outcomes. RESULTS: In total 291 patients were included in the analysis: 197 in the TEE-guided group and 94 in the fluoroscopy-guided group. Fluoroscopy-guided procedures were markedly shorter (48 ± 20 min vs. 25 ± 9 min; p < .01). There was no difference in procedural complications, including death, major bleeding, device dislodgement, stroke or clinically relevant peripheral embolization between the two groups (.5% vs. 0%; p = .99). Hospital stay was also shorter with the simplified approach (2.5 ± 1.6 vs. 3.5 ± 1.2 days; p < .01), allowing 85% same-day discharges during the last 12 months of observation period. At 6 ± 3 months echocardiographic follow-up a residual leakage was described in 8% of the TEE-guided cases and 2% of the fluoroscopy-guided cases (p = .08). CONCLUSION: While a complete TEE-free PFO closure might have potential procedural risks, our approach of pure fluoroscopy-guided with a brisk final TEE check seems to be advantageous in terms of procedural aspects with no sign of any acute or intermediate-term hazard and it could offer an equitable compromise between the two worlds: a complete TEE procedure and a procedure without any TEE.

VA-ECMO and thrombus aspiration in a pulmonary embolism patient with cardiac arrest and contraindications to thrombolytic therapy.

A 57-year-old male patient with a history of proximal deep vein thrombosis on vitamin K antagonist therapy, suffered a recent hypertensive intracranial hemorrhage without significant neurological deficit. Three weeks later he presented with bilateral central pulmonary embolism. He had witnessed cardiac arrest and was put on veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Endovascular thrombectomy with an Aspirex device led to a significant improvement of hemodynamics. VA-ECMO was terminated after one day, an IVC filter was inserted, and he was discharged from ICU after 15 days. In conclusion, VA-ECMO and endovascular therapy are rescue strategies in patients with contraindications for thrombolysis.

Impact of the Choice of Native T1 in Pixelwise Myocardial Blood Flow Quantification.

BACKGROUND: Quantification of myocardial blood flow (MBF) from dynamic contrast-enhanced (DCE) MRI can be performed using a signal intensity model that incorporates T1 values of blood and myocardium. PURPOSE: To assess the impact of T1 values on pixelwise MBF quantification, specifically to evaluate the influence of 1) study population-averaged vs. subject-specific, 2) diastolic vs. systolic, and 3) regional vs. global myocardial T1 values. STUDY TYPE: Prospective. SUBJECTS: Fifteen patients with chronic coronary heart disease. FIELD STRENGTH/SEQUENCE: 3T; modified Look-Locker inversion recovery for T1 mapping and saturation recovery gradient echo for DCE imaging, both acquired in a mid-ventricular short-axis slice in systole and diastole. ASSESSMENT: MBF was estimated using Fermi modeling and signal intensity nonlinearity correction with different T1 values: study population-averaged blood and myocardial, subject-specific systolic and diastolic, and segmental T1 values. Myocardial segments with perfusion deficits were identified visually from DCE series. STATISTICAL TESTS: The relationships between MBF parameters derived by different methods were analyzed by Bland-Altman analysis; corresponding mean values were compared by t-test. RESULTS: Using subject-specific diastolic T1 values, global diastolic MBF was 0.61 ± 0.13 mL/(min·g). It did not differ from global MBF derived from the study population-averaged T1 (P = 0.88), but the standard deviation of differences was large (0.07 mL/(min·g), 11% of mean MBF). Global diastolic and systolic MBF did not differ (P = 0.12), whereas global diastolic MBF using systolic (0.62 ± 0.13 mL/(min·g)) and diastolic T1 values differed (P < 0.05). If regional instead of global T1 values were used, segmental MBF was lower in segments with perfusion deficits (bias = -0.03 mL/(min·g), -7% of mean MBF, P < 0.05) but higher in segments without perfusion deficits (bias = 0.01 mL/(min·g), 1% of mean MBF, P < 0.05). DATA CONCLUSION: Whereas cardiac phase-specific T1 values have a minor impact on MBF estimates, subject-specific and myocardial segment-specific T1 values substantially affect MBF quantification. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 3.

Mobile Eye-Tracking Data Analysis Using Object Detection via YOLO v4.

Remote eye tracking has become an important tool for the online analysis of learning processes. Mobile eye trackers can even extend the range of opportunities (in comparison to stationary eye trackers) to real settings, such as classrooms or experimental lab courses. However, the complex and sometimes manual analysis of mobile eye-tracking data often hinders the realization of extensive studies, as this is a very time-consuming process and usually not feasible for real-world situations in which participants move or manipulate objects. In this work, we explore the opportunities to use object recognition models to assign mobile eye-tracking data for real objects during an authentic students' lab course. In a comparison of three different Convolutional Neural Networks (CNN), a Faster Region-Based-CNN, you only look once (YOLO) v3, and YOLO v4, we found that YOLO v4, together with an optical flow estimation, provides the fastest results with the highest accuracy for object detection in this setting. The automatic assignment of the gaze data to real objects simplifies the time-consuming analysis of mobile eye-tracking data and offers an opportunity for real-time system responses to the user's gaze. Additionally, we identify and discuss several problems in using object detection for mobile eye-tracking data that need to be considered.

Automated mitral valve vortex ring extraction from 4D-flow MRI.

PURPOSE: To present and validate a method for automated extraction and analysis of the temporal evolution of the mitral valve (MV) vortex ring from MR 4D-flow data. METHODS: The proposed algorithm uses the divergence-free part of the velocity vector field for Q criterion-based identification and tracking of MV vortex ring core and region within the left ventricle (LV). The 4D-flow data of 20 subjects (10 healthy controls, 10 patients with ischemic heart disease) were used to validate the algorithm against visual analysis as well as to assess the method's sensitivity to manual LV segmentation. Quantitative MV vortex ring parameters were analyzed with respect to both their differences between healthy subjects and patients and their correlation with transmitral peak velocities. RESULTS: The algorithm successfully extracted MV vortex rings throughout the entire cardiac cycle, which agreed substantially with visual analysis (Cohen's kappa = 0.77). Furthermore, vortex cores and regions were robustly detected even if a static end-diastolic LV segmentation mask was applied to all frames (Dice coefficients 0.82 ± 0.08 and 0.94 ± 0.02 for core and region, respectively). Early diastolic MV vortex ring vorticity, kinetic energy and circularity index differed significantly between healthy controls and patients. In contrast to vortex shape parameters, vorticity and kinetic energy correlated strongly with transmitral peak velocities. CONCLUSION: An automated method for temporal MV vortex ring extraction demonstrating robustness with respect to LV segmentation strategies is introduced. Quantitative vortex parameter analysis indicates importance of the MV vortex ring for LV diastolic (dys)function.

Empagliflozin protects heart from inflammation and energy depletion via AMPK activation.

AIMS: Sodium-glucose co-transporter 2 (SGLT2) were originally developed as kidney-targeting anti-diabetic drugs. However, due to their beneficial cardiac off-target effects (as SGLT2 is not expressed in the heart), these antagonists currently receive intense clinical interest in the context of heart failure (HF) in patients with or without diabetes mellitus (DM). Since the mechanisms by which these beneficial effects are mediated are still unclear yet, inflammation that is present in DM and HF has been proposed as a potential pharmacological intervention strategy. Therefore, we tested the hypothesis that the SGLT2 inhibitor, empagliflozin, displays anti-inflammatory potential along with its glucose-lowering property. METHODS AND RESULTS: Lipopolysaccharide (LPS) was used to induce inflammation in vitro and in vivo. In cardiomyocytes and macrophages empagliflozin attenuated LPS-induced TNFα and iNOS expression. Analysis of intracellular signalling pathways suggested that empagliflozin activates AMP kinase (AMPK) in both cell types with or without LPS-treatment. Moreover, the SGLT2 inhibitor increased the expression of anti-inflammatory M2 marker proteins in LPS-treated macrophages. Additionally, empagliflozin-mediated AMPK activation prevented LPS-induced ATP/ADP depletion. In vivo administration of LPS in mice impaired cardiac contractility and aortic endothelial relaxation in response to acetylcholine, whereby co-administration of empagliflozin preserved cardiovascular function. These findings were accompanied by improved cardiac AMPK phosphorylation and ATP/ADP, reduced cardiac iNOS, plasma TNFα and creatine kinase MB levels. CONCLUSION: Our data identify a novel cardio protective mechanism of SGLT2 inhibitor, empagliflozin, suggesting that AMPK activation-mediated energy repletion and reduced inflammation contribute to the observed cardiovascular benefits of the drug in HF.

Atrial fibrillation in transcatheter aortic valve implantation patients: Incidence, outcome and predictors of new onset.

BACKGROUND: There is controversial evidence if atrial fibrillation (AF) alters outcome after transcatheter aortic valve implantation (TAVI). TAVI itself may promote new-onset AF (NOAF). METHODS: We performed a single-center study including 398 consecutive patients undergoing TAVI. Before TAVI, patients were divided into a sinus rhythm (SR) group (n=226, 57%) and baseline AF group (n=172, 43%) according to clinical records and electrocardiograms. Furthermore, incidence and predictors of NOAF were recorded. RESULTS: Baseline AF patients had a significantly higher 1-year mortality than the baseline SR group (19.8% vs. 11.5%, p=0.02). NOAF occurred in 7.1% of patients with prior SR. Previous valve surgery was the only significant predictor of NOAF (HR 5.86 [1.04-32.94], p<0.05). NOAF was associated with higher rehospitalization rate (62.5 vs. 34.8%, p=0.04), whereas mortality was unaffected. CONCLUSIONS: This study shows that NOAF is associated with higher rates of rehospitalization but not mortality after TAVI. Overall, patients with pre-existing AF have higher mortality.

G0/G1 Switch Gene 2 Regulates Cardiac Lipolysis.

The anabolism and catabolism of myocardial triacylglycerol (TAG) stores are important processes for normal cardiac function. TAG synthesis detoxifies and stockpiles fatty acids to prevent lipotoxicity, whereas TAG hydrolysis (lipolysis) remobilizes fatty acids from endogenous storage pools as energy substrates, signaling molecules, or precursors for complex lipids. This study focused on the role of G0/G1 switch 2 (G0S2) protein, which was previously shown to inhibit the principal TAG hydrolase adipose triglyceride lipase (ATGL), in the regulation of cardiac lipolysis. Using wild-type and mutant mice, we show the following: (i) G0S2 is expressed in the heart and regulated by the nutritional status with highest expression levels after re-feeding. (ii) Cardiac-specific overexpression of G0S2 inhibits cardiac lipolysis by direct protein-protein interaction with ATGL. This leads to severe cardiac steatosis. The steatotic hearts caused by G0S2 overexpression are less prone to fibrotic remodeling or cardiac dysfunction than hearts with a lipolytic defect due to ATGL deficiency. (iii) Conversely to the phenotype of transgenic mice, G0S2 deficiency results in a de-repression of cardiac lipolysis and decreased cardiac TAG content. We conclude that G0S2 acts as a potent ATGL inhibitor in the heart modulating cardiac substrate utilization by regulating cardiac lipolysis.

Functional and molecular factors associated with TAPSE in hypoxic pulmonary hypertension.

Adaptation of the right ventricle (RV) to increased afterload is crucial for survival in pulmonary hypertension (PH), but it is challenging to assess RV function and identify associated molecular mechanisms. The aim of the current study was to analyze the relationship between invasive and noninvasive parameters of RV morphology and function and associated molecular changes. The response of mice to normobaric hypoxia was assessed by hechocardiography, invasive hemodynamics, and histological and molecular analyses. Plasma levels of possibly novel markers of RV remodeling were measured by ELISA in patients with idiopathic pulmonary arterial hypertension (IPAH) and matched healthy controls. Chronic hypoxia-induced PH was accompanied by significantly decreased tricuspid annular plane systolic excursion (TAPSE) and unchanged RV contractility index and tau. RV hypertrophy was present without an increase in fibrosis. There was no change in α- and ß-major histocompatibility class or natriuretic peptides expression. Comparative microarray analysis identified two soluble factors, fibroblast growth factor-5 (FGF5) and interleukin-22 receptor alpha-2 (IL22RA2), as being possibly associated with RV remodeling. We observed significantly higher plasma levels of IL22RA2, but not FGF5, in patients with IPAH. Hypoxic pulmonary hypertension in a stage of RV remodeling with preserved systolic function is associated with decreased pulmonary vascular compliance, mild diastolic RV dysfunction, and significant decrease in TAPSE. Subtle gene expression changes in the RV vs. the left ventricle upon chronic hypoxia suggest that the majority of changes are due to hypoxia and not due to changes in afterload. Increased IL22RA2 levels might represent a novel RV adaptive mechanism.

Early remodeling of perinuclear Ca2+ stores and nucleoplasmic Ca2+ signaling during the development of hypertrophy and heart failure.

BACKGROUND: A hallmark of heart failure is impaired cytoplasmic Ca(2+) handling of cardiomyocytes. It remains unknown whether specific alterations in nuclear Ca(2+) handling via altered excitation-transcription coupling contribute to the development and progression of heart failure. METHODS AND RESULTS: Using tissue and isolated cardiomyocytes from nonfailing and failing human hearts, as well as mouse and rabbit models of hypertrophy and heart failure, we provide compelling evidence for structural and functional changes of the nuclear envelope and nuclear Ca(2+) handling in cardiomyocytes as remodeling progresses. Increased nuclear size and less frequent intrusions of the nuclear envelope into the nuclear lumen indicated altered nuclear structure that could have functional consequences. In the (peri)nuclear compartment, there was also reduced expression of Ca(2+) pumps and ryanodine receptors, increased expression of inositol-1,4,5-trisphosphate receptors, and differential orientation among these Ca(2+) transporters. These changes were associated with altered nucleoplasmic Ca(2+) handling in cardiomyocytes from hypertrophied and failing hearts, reflected as increased diastolic Ca(2+) levels with diminished and prolonged nuclear Ca(2+) transients and slowed intranuclear Ca(2+) diffusion. Altered nucleoplasmic Ca(2+) levels were translated to higher activation of nuclear Ca(2+)/calmodulin-dependent protein kinase II and nuclear export of histone deacetylases. Importantly, the nuclear Ca(2+) alterations occurred early during hypertrophy and preceded the cytoplasmic Ca(2+) changes that are typical of heart failure. CONCLUSIONS: During cardiac remodeling, early changes of cardiomyocyte nuclei cause altered nuclear Ca(2+) signaling implicated in hypertrophic gene program activation. Normalization of nuclear Ca(2+) regulation may therefore be a novel therapeutic approach to prevent adverse cardiac remodeling.

Functional cardiac lipolysis in mice critically depends on comparative gene identification-58.

Efficient catabolism of cellular triacylglycerol (TG) stores requires the TG hydrolytic activity of adipose triglyceride lipase (ATGL). The presence of comparative gene identification-58 (CGI-58) strongly increased ATGL-mediated TG catabolism in cell culture experiments. Mutations in the genes coding for ATGL or CGI-58 in humans cause neutral lipid storage disease characterized by TG accumulation in multiple tissues. ATGL gene mutations cause a severe phenotype especially in cardiac muscle leading to cardiomyopathy that can be lethal. In contrast, CGI-58 gene mutations provoke severe ichthyosis and hepatosteatosis in humans and mice, whereas the role of CGI-58 in muscle energy metabolism is less understood. Here we show that mice lacking CGI-58 exclusively in muscle (CGI-58KOM) developed severe cardiac steatosis and cardiomyopathy linked to impaired TG catabolism and mitochondrial fatty acid oxidation. The marked increase in ATGL protein levels in cardiac muscle of CGI-58KOM mice was unable to compensate the lack of CGI-58. The addition of recombinant CGI-58 to cardiac lysates of CGI-58KOM mice completely reconstituted TG hydrolytic activities. In skeletal muscle, the lack of CGI-58 similarly provoked TG accumulation. The addition of recombinant CGI-58 increased TG hydrolytic activities in control and CGI-58KOM tissue lysates, elucidating the limiting role of CGI-58 in skeletal muscle TG catabolism. Finally, muscle CGI-58 deficiency affected whole body energy homeostasis, which is caused by impaired muscle TG catabolism and increased cardiac glucose uptake. In summary, this study demonstrates that functional muscle lipolysis depends on both CGI-58 and ATGL.

Associations of methylarginines and homoarginine with diastolic dysfunction and cardiovascular risk factors in patients with preserved left ventricular ejection fraction.

BACKGROUND: Asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and homoarginine are considered to modulate nitric oxide synthesis. We evaluated whether ADMA, SDMA, and homoarginine are associated with diastolic dysfunction. METHODS AND RESULTS: We investigated primary care patients at cardiovascular risk with preserved left ventricular ejection fraction from the multicenter DIAST-CHF study. We measured serum concentrations of ADMA, SDMA, and homoarginine and performed standardized echocardiographic examinations. Among 1,396 patients (mean age 65.3 ± 8.3 y, 54.6% women), diastolic dysfunction was ruled out in 261 patients (18.7%). Mild and moderate/severe grades of diastolic dysfunction were present in 900 (64.5%) and 235 (16.8%) study participants, respectively. After adjustments for cardiovascular risk factors, ADMA and SDMA were positively and homoarginine negatively associated with N-terminal pro-B-type natriuretic peptide and midregional pro-adrenomedullin (P < .05 for all). Lower homoarginine levels were associated with diastolic dysfunction, and higher ADMA and SDMA levels were associated with the severity of diastolic dysfunction (P < .05 for all). CONCLUSIONS: Higher levels of ADMA and SDMA and lower levels of homoarginine are associated with an adverse cardiovascular risk profile and diastolic dysfunction. Further studies should clarify the potential of these amino acid derivatives for the therapy of cardiovascular diseases.

A refined approach for evaluating small datasets via binary classification using machine learning.

Classical statistical analysis of data can be complemented or replaced with data analysis based on machine learning. However, in certain disciplines, such as education research, studies are frequently limited to small datasets, which raises several questions regarding biases and coincidentally positive results. In this study, we present a refined approach for evaluating the performance of a binary classification based on machine learning for small datasets. The approach includes a non-parametric permutation test as a method to quantify the probability of the results generalising to new data. Furthermore, we found that a repeated nested cross-validation is almost free of biases and yields reliable results that are only slightly dependent on chance. Considering the advantages of several evaluation metrics, we suggest a combination of more than one metric to train and evaluate machine learning classifiers. In the specific case that both classes are equally important, the Matthews correlation coefficient exhibits the lowest bias and chance for coincidentally good results. The results indicate that it is essential to avoid several biases when analysing small datasets using machine learning.

Impact of the evaluation method on 4D flow-derived diastolic transmitral and myocardial peak velocities: Comparison with echocardiography.

PURPOSE: To compare agreement of different evaluation methods of magnetic resonance (MR) 4D flow-derived diastolic transmitral and myocardial peak velocities as well as their ratios, using echocardiography as reference. METHODS: In this prospective study, 60 subjects without symptoms of cardiovascular disease underwent echocardiography and non-contrast 3 T MR 4D flow imaging of the heart. Early- (E) and late-diastolic (A) transmitral peak filling velocities were evaluated from 4D flow data using three different strategies: 1) at the mitral valve tips in short-axis orientation (SA-method), 2) between the mitral valve tips in 4-chamber orientation (4-chamber-method), and 3) as maximal velocities in the transmitral inflow volume (max-velocity-method). Septal, lateral and average early-diastolic myocardial peak velocities (e') were derived from the myocardial tissue in the vicinity of the mitral valve. 4D flow parameters were compared with echocardiography by correlation and Bland-Altman analysis. RESULTS: All 4D flow-derived E, A and E/A values correlated with echocardiography (r = 0.65-0.73, 0.75-0.83 and 0.74-0.86, respectively). While the SA- and 4-chamber-methods substantially underestimated E and A compared to echocardiography (p < 0.001), the max-velocity-method provided E (p = 0.13) and E/A (p = 0.07) without significant bias. Septal, lateral and average e' from 4D flow as well as the max-velocity-method-derived E/e' correlated with echocardiographic measurements (r = 0.64-0.81) and showed no significant bias (p = 0.26-0.54). CONCLUSION: MR 4D flow imaging allows precise and accurate evaluation of transmitral and myocardial peak velocities for characterization of LV diastolic function without significant bias to echocardiography, when transmitral velocities are assessed from the transmitral inflow volume. This enables the use of validated echocardiography threshold values.

Operator decision-making in angiography-only guided revascularization for lesions not indicated for FFR: a QFR-based functional assessment in chronic coronary syndrome.

Background: Discordance between coronary angiographic findings and invasive functional significance is well-established. Yet, the prevalence of this mismatch in an era increasingly utilizing invasive functional assessments, such as fractional flow reserve (FFR), remains unclear. This study examines the extent of such discrepancies in current clinical practice. Methods: This single-center prospective registry included consecutive patients with chronic coronary syndrome (CCS) who underwent elective coronary angiography, with or without revascularization. Coronary angiograms deemed not requiring FFR due to clear anatomical distinctions, either anatomically severe indicating a need for revascularization or mild suggesting no need for intervention, were selected for evaluation. These were then subjected to post-hoc analysis by three independent operators who were blinded to the definitive treatment strategies. Importantly, the post-hoc analysis was conducted in two distinct phases: firstly, a re-evaluation of coronary stenosis, and secondly, a separate functional assessment, each carried out independently. Coronary stenosis severity was assessed visually, while functional relevance was determined by quantitative flow ratio (QFR), calculated using a computational fluid dynamics algorithm applied to angiographic images. Analysis focused on discrepancies between QFR-based functional indications and revascularization strategies actually performed. Results: In 191 patients, 488 vessels were analyzed. Average diameter stenosis (DS) was 37 ± 34%, and QFR was 0.87 ± 0.15, demonstrating a moderate correlation (r = -0.84; 95% CI: -0.86 to -0.81, p < 0.01). Agreement with QFR at conventional anatomical cutoffs was 88% for 50% DS and 91% for 70% DS. Mismatches between revascularization decisions and QFR indications occurred in 10% of cases. Discrepancies were more frequent in the left anterior descending artery (14%) compared to the left circumflex (6%) and the right coronary artery (9%; p = 0.07). Conclusion: In a cardiac-center where FFR utilization is high, discordance between coronary angiography and functional significance persists, even when operators are confident in their decisions not to use functional interrogation. This gap, most evident in the left anterior descending artery, highlights the potential need for integrated angiography-based functional assessments to refine revascularization decisions in CCS.

A Neuronal Network-Based Score Predicting Survival in Patients Undergoing Aortic Valve Intervention: The ABC-AS Score.

Background: Despite being the most commonly performed valvular intervention, risk prediction for aortic valve replacement in patients with severe aortic stenosis by currently used risk scores remains challenging. The study aim was to develop a biomarker-based risk score by means of a neuronal network. Methods: In this multicenter study, 3595 patients were divided into test and validation cohorts (70% to 30%) by random allocation. Input variables to develop the ABC-AS score were age, the cardiac biomarker high-sensitivity troponin T, and a patient history of cardiac decompensation. The validation cohort was used to verify the scores' value and for comparison with the Society of Thoracic Surgery Predictive Risk of Operative Mortality score. Results: Receiver operating curves demonstrated an improvement in prediction by using the ABC-AS score compared to the Society of Thoracic Surgery Predictive Risk of Operative Mortality (STS prom) score. Although the difference in predicting cardiovascular mortality was most notable at 30-day follow-up (area under the curve of 0.922 versus 0.678), ABC-AS also performed better in overall follow-up (0.839 versus 0.699). Furthermore, univariate analysis of ABC-AS tertiles yielded highly significant differences for all-cause (p < 0.0001) and cardiovascular mortality (p < 0.0001). Head-to-head comparison between both risk scores in a multivariable cox regression model underlined the potential of the ABC-AS score (HR per z-unit 2.633 (95% CI 2.156-3.216), p < 0.0001), while the STS prom score failed to reach statistical significance (p = 0.226). Conclusions: The newly developed ABC-AS score is an improved risk stratification tool to predict cardiovascular outcomes for patients undergoing aortic valve intervention.

Impact of the Timing of Mechanical Circulatory Support on the Outcomes in Myocardial Infarction-Related Cardiogenic Shock: Subanalysis of the PREPARE CS Registry.

(1) Background: Mechanical circulatory support (MCS) in myocardial infarction-associated cardiogenic shock is subject to debate. This analysis aims to elucidate the impact of MCS's timing on patient outcomes, based on data from the PREPARE CS registry. (2) Methods: The PREPARE CS prospective registry includes patients who experienced cardiogenic shock (SCAI classes C-E) and were subsequently referred for cardiac catheterization. Our present analysis included a subset of this registry, in whom MCS was used and who underwent coronary intervention due to myocardial infarction. Patients were categorized into an Upfront group and a Procedural group, depending on the timing of MCS's introduction in relation to their PCI. The endpoint was in-hospital mortality. (3) Results: In total, 71 patients were included. MCS was begun prior to PCI in 33 (46%) patients (Upfront), whereas 38 (54%) received MCS during or after the initiation of PCI (Procedural). The groups' baseline characteristics and hemodynamic parameters were comparable. The Upfront group had a higher utilization of the Impella® device compared to extracorporeal membrane oxygenation (67% vs. 33%), while the Procedural group exhibited a balanced use of both (50% vs. 50%). Most patients suffered from multi-vessel disease in both groups (82% vs. 84%, respectively; p = 0.99), and most patients required a complex PCI procedure; the latter was more prevalent in the Upfront group (94% vs. 71%, respectively; p = 0.02). Their rates of complete revascularization were comparable (52% vs. 34%, respectively; p = 0.16). Procedural CPR was significantly more frequent in the Procedural group (45% vs. 79%, p < 0.05); however, in-hospital mortality was similar (61% vs. 79%, respectively; p = 0.12). (4) Conclusions: The upfront implantation of MCS in myocardial infarction-associated CS did not provide an in-hospital survival benefit.